Serine protease activity is essential for thrombin-induced protein synthesis in cultured human dental pulp cells: modulation roles of prostaglandin E2.
Irritations and injuries to the dental pulp usually lead to different degrees of pulpal inflammation. To investigate the roles of thrombin and prostaglandins in the healing and inflammatory processes of dental pulp as well as their effects on pulpal protein synthesis, human dental pulp cell cultures were established and their protein production was measured with or without the presence of exogenous thrombin and prostaglandins. At concentrations of 1-25 U/ml, alpha-thrombin increased the protein synthesis to 1.4-2.3 fold over the vehicle control. On the contrary, 0.1 microg/ml of prostaglandin E1 (PGE1) suppressed protein synthesis by 60%. Prostaglandin E2 (PGE2) also inhibited protein synthesis with an IC50 of 0.4 microg/ml. The stimulatory effects of thrombin (10 U/ml) can be inhibited by antithrombin III (2 U/ml) (a natural thrombin inhibitor) with heparin (2 U/ml), PPACK (D-Phe-Pro-ArgCH2Cl) (20-50 microg/ml) (a serine protease inhibitor), and PGE2 (0.5-1.0 microg/ml). Moreover, TRAP (20-40 microg/ml), a thrombin receptor agonist peptide, also exerted a stimulatory effect (1.21-1.37 fold). In conclusion, thrombin-induced protein synthesis by pulp cells is dependent on proteolytic activity, but not on binding to receptors. Both PGE1 and PGE2 exert suppressive effects on protein synthesis, indicating that interactions between thrombin and prostaglandins are important in regulating the inflammation, repair and regeneration of pulp tissue following injury.
Chang
M C
MC
Team of Biomedical Science, Chang-Gung Institute of Nursing, Taoyuan, Taiwan.
Lan
W H
WH
Chan
C P
CP
Lin
C P
CP
Hsieh
C C
CC
Jeng
J H
JH
D000328:Adult; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D055232:Proline-Rich Protein Domains; D014176:Protein Biosynthesis; D012038:Regeneration / Q000502:physiology; D012044:Regression Analysis; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D013268:Stimulation, Chemical; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology
D010455:Peptides; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D013917:Thrombin; D015232:Dinoprostone